The broad aim of this Grand Opportunity Grant is to understand how race-based social stress, racial/ethnic (R/E) identity, and biological functioning contribute to health and healthy aging. Using the Maryland Adolescent Development in Context Study (MADICS) we propose to complement existing psychosocial, mental, and physical health data with the collection of a comprehensive set of measures of biological systems intimately tied to health and disease and highly relevant to the aging processes. MADICS is a nationally-recognized 17- year longitudinal study of family, school, neighborhood, and peer influences on the healthy and successful development of an initial sample of 1482 early adolescents and their families (60% African American, 35% European American, and similar proportions of "middle class" SES within these groups). Measures gathered across seven waves of data collection (ages 12 to 30) include histories of perceived discrimination based on race/ethnicity;beliefs, behaviors, and feelings about one's perceived R/E classification (i.e., R/E identity);mental and physical health;and psychosocial functioning (e.g., educational and occupational attainment). Here we propose to add a wide range of measures of biological systems associated with health and disease and highly relevant to the prospective study of aging processes. The primary goal is to explore how developmental histories of discrimination contribute to the pre-disease and health states of approximately 300 young adults (approximately 32 years old) and the extent to which these relations vary by R/E classification, SES, and R/E identity. Specifically, we will assess (1) the basal functioning of multiple physiological systems (endocrine, cardiovascular, metabolic, immune, inflammatory, sleep) reflecting well-established risk factors for a variety of poor health outcomes;(2) the acute reactivity and recovery of three physiological response systems tied to the development of chronic disease (i.e., hypothalamic-pituitary-adrenal [HPA] axis, autonomic nervous system, inflammatory system) in the context of a daily diary study and also in an experimental setting in which we expose individuals to a discriminatory episode;(3) inflammatory cytokine production and immune cell resistance to the anti-inflammatory effects of glucocorticoids, gene expression profiling of leukocytes to identify broad groups of genes associated with social stress (e.g., inflammation-related genes), and bioinformatic analyses to identify transcriptional control pathways that might potentially mediate these effects;and (4) person-centered health trajectory profiles constructed from mental and physical health and the proposed biomarkers and the extent to which their relations to histories of discrimination are moderated by R/E classification, SES, R/E identity, and parent socialization factors. An additional aim of this grant is to develop methods that can become part of the toolkit of future field-based health and aging researchers (e.g., validation of the measurement of TNF-alpha and IL6 in Oral Mucosal Transudate and the development of a field-friendly stress reactivity protocol that can be conducted in a mobile psychophysiological van). PUBLIC HEALTH RELEVANCE: Disparities in health associated with racial/ethnic classification persist in the US. The elimination of such health disparities is of paramount importance for public health. Understanding factors associated with health disparities is critical for their elimination. This application includes studies that focus on better understanding the biological, psychological, and social factors that contribute to health disparities.